Gerry Nicolaes

Associate professor

Dr Gerry Nicolaes received a Masters’ degree in Chemistry from the Utrecht University with majors in clinical chemistry, biochemistry and protein engineering and enzymology. He obtained a PhD from the Maastricht University on the regulation of thrombin formation in normal and hypercoagulable plasma (with Prof. H.C. Hemker) and later spent several years at the laboratory of Prof. B. Dahlbäck at the Lund University (Sweden), focussing on the use of molecular biological technologies in blood coagulation research.

Dr Nicolaes received a Vidi grant by the Netherlands Organisation for Scientific Research (NWO) to establish a research line that uses structural bioinformatics to rationally approach the structure-function study of proteins involved in coagulation and inflammation. In addition to protein structure-function research, in recent years, in silico drug design and optimisation of biologically active molecules for use in therapy or diagnosis has become one of the major research focusses.

His research interests are within the fields of thrombosis and haemostasis, and in particular on the overlap with the fields of inflammation and atherosclerosis. In this respect, extracellular histones and their role in systemic inflammatory disease and sepsis have evolved into a major research focus.

He is the president of the Netherlands Society on Biomolecular Modelling.

Dr Nicolaes has published more than 80 peer reviewed research papers, has been a co-promotor of 7 successful PhD students and currently supervises 7 more PhD students. He is inventor of several granted patents.

Department of Biochemistry
Universiteitsingel 50, 6229 ER Maastricht
PO Box 616, 6200 MD Maastricht
Room number: 4.352

  • 2020
    • Graca, N. A. G., Ercig, B., Pereira, L. C. V., Kangro, K., Kaijen, P., Nicolaes, G. A. F., Veyradier, A., Coppo, P., Vanhoorelbeke, K., Mannik, A., & Voorberg, J. (2020). Modifying ADAMTS13 to modulate binding of pathogenic autoantibodies of patients with acquired thrombotic thrombocytopenic purpura. Haematologica-the Hematology Journal, 105(11), 2619-2630. https://doi.org/10.3324/haematol.2019.226068
    • Beurskens, D. M. H., Huckriede, J. P., Schrijver, R., Hemker, H. C., Reutelingsperger, C. P., & Nicolaes, G. A. F. (2020). The Anticoagulant and Nonanticoagulant Properties of Heparin. Thrombosis and Haemostasis, 120(10), 1371-1383. https://doi.org/10.1055/s-0040-1715460
    • Bol, M. E., Beurskens, D. M. H., Delnoij, T. S. R., Roekaerts, P. M. H. J., Reutelingsperger, C. P. M., Delhaas, T., van de Poll, M. C. G., Sels, J-W. E. M., & Nicolaes, G. A. F. (2020). Variability of Microcirculatory Measurements in Critically Ill Patients. Shock, 54(1), 9-14. https://doi.org/10.1097/SHK.0000000000001470
    • Beurskens, D. M. H., Bol, M. E., Delhaas, T., van de Poll, M. C. G., Reutelingsperger, C. P. M., Nicolaes, G. A. F., & Sels, J-W. E. M. (2020). Decreased endothelial glycocalyx thickness is an early predictor of mortality in sepsis. Anaesthesia and Intensive Care, 48(3), 221-228. https://doi.org/10.1177/0310057X20916471
    • Tas, J., van Gassel, R. J. J., Heines, S. J. H., Mulder, M. M. G., Heijnen, N. F. L., Acampo-de Jong, M. J., Bels, J. L. M., Bennis, F. C., Koelmann, M., Groven, R. V. M., Donkers, M. A., van Rosmalen, F., Hermans, B. J. M., Meex, S. J. R., Mingels, A., Bekers, O., Savelkoul, P., Oude Lashof, A. M. L., Wildberger, J., ... van Bussel, B. C. T. (2020). Serial measurements in COVID-19-induced acute respiratory disease to unravel heterogeneity of the disease course: design of the Maastricht Intensive Care COVID cohort (MaastrICCht). BMJ Open, 10(9), [040175]. https://doi.org/10.1136/bmjopen-2020-040175
  • 2019
    • Sang, Y., Huskens, D., Wichapong, K., de Laat, B., Nicolaes, G. A. F., & Roest, M. (2019). A Synthetic Triple Helical Collagen Peptide as a New Agonist for Flow Cytometric Measurement of GPVI-Specific Platelet Activation. Thrombosis and Haemostasis, 119(12), 2005-2013. https://doi.org/10.1055/s-0039-1697660
    • Bohler, S., Liu, X., Krauskopf, J., Gaiment, F., Aubrecht, J., Nicolaes, G. A. F., Kleinjans, J. C. S., & Briede, J. J. (2019). Acetaminophen Overdose as a Potential Risk Factor for Parkinson's Disease. Clinical Pharmacology & Therapeutics, 106(4), 696-696. https://doi.org/10.1111/cts.12663
    • Silvestre-Roig, C., Braster, Q., Wichapong, K., Lee, E. Y., Marie Teulon, J., Berrebeh, N., Winter, J., Adrover, J. M., Santos, G. S., Froese, A., Lemnitzer, P., Ortega-Gomez, A., Chevre, R., Marschner, J., Schumski, A., Winter, C., Perez-Olivares, L., Pan, C., Paulin, N., ... Soehnlein, O. (2019). Externalized histone H4 orchestrates chronic inflammation by inducing lytic cell death. Nature, 569(7755), 236-240. https://doi.org/10.1038/s41586-019-1167-6
    • Wichapong, K., Poelman, H., Ercig, B., Hrdinova, J., Liu, X., Lutgens, E., & Nicolaes, G. A. F. (2019). Rational modulator design by exploitation of protein-protein complex structures. Future Medicinal Chemistry, 11(9), 1015-1033. https://doi.org/10.4155/fmc-2018-0433
    • Seijkens, T. T. P., Poels, K., Meiler, S., van Tiel, C. M., Kusters, P. J. H., Reiche, M., Atzler, D., Winkels, H., Tjwa, M., Poelman, H., Slutter, B., Kuiper, J., Gijbels, M., Kuivenhoven, J. A., Matic, L. P., Paulsson-Berne, G., Hedin, U., Hansson, G. K., Nicolaes, G. A. F., ... Lutgens, E. (2019). Deficiency of the T cell regulator Casitas B-cell lymphoma-B aggravates atherosclerosis by inducing CD8(+) T cell-mediated macrophage death. European Heart Journal, 40(4), 372-382. https://doi.org/10.1093/eurheartj/ehy714
    • Astuti, P., Beurskens, D., Vajen, T., Nicolaes, G., Zhang, M., & Guido, H. (2019). Protection against neutrophil extracellular trap (NET) toxicity by antioxidant monoHER. Makara Journal of Health Research, 23(2), 108-115. https://doi.org/10.7454/msk.v23i2.10453
  • 2018
    • Braza, M. S., van Leent, M. M. T., Lameijer, M., Sanchez-Gaytan, B. L., Arts, R. J. W., Perez-Medina, C., Conde, P., Garcia, M. R., Gonzalez-Perez, M., Brahmachary, M., Fay, F., Kluza, E., Kossatz, S., Dress, R. J., Salem, F., Rialdi, A., Reiner, T., Boros, P., Strijkers, G. J., ... Ochando, J. (2018). Inhibiting Inflammation with Myeloid Cell-Specific Nanobiologics Promotes Organ Transplant Acceptance. Immunity, 49(5), 819-828.e6. https://doi.org/10.1016/j.immuni.2018.09.008
    • Schelpe, A-S., Orlando, C., Ercig, B., Geeroms, C., Pareyn, I., Vandeputte, N., Pereira, L. C., Roose, E., Fostier, K., Nicolaes, G. A. F., Deckmyn, H., De Meyer, S. F., Vanhoorelbeke, K., & Jochmans, K. (2018). Child-onset thrombotic thrombocytopenic purpura caused by p.R498C and p.G259PfsX133 mutations in ADAMTS13. European Journal of Haematology, 101(2), 191-199. https://doi.org/10.1111/ejh.13094
    • Winter, C., Silvestre-Roig, C., Ortega-Gomez, A., Lemnitzer, P., Poelman, H., Schumski, A., Winter, J., Drechsler, M., de Jong, R., Immler, R., Sperandio, M., Hristov, M., Zeller, T., Nicolaes, G. A. F., Weber, C., Viola, J. R., Hidalgo, A., Scheiermann, C., & Soehnlein, O. (2018). Chrono-pharmacological Targeting of the CCL2-CCR2 Axis Ameliorates Atherosclerosis. Cell Metabolism, 28(1), 175-182.e5. https://doi.org/10.1016/j.cmet.2018.05.002
    • Seijkens, T. T. P., van Tiel, C. M., Kusters, P. J. H., Atzler, D., Soehnlein, O., Zarzycka, B., Aarts, S. A. B. M., Lameijer, M., Gijbels, M. J., Beckers, L., den Toom, M., Slutter, B., Kuiper, J., Duchene, J., Aslani, M., Megens, R. T. A., van 't Veer, C., Kooij, G., Schrijver, R., ... Lutgens, E. (2018). Targeting CD40-Induced TRAF6 Signaling in Macrophages Reduces Atherosclerosis. Journal of the American College of Cardiology, 71(5), 527-542. https://doi.org/10.1016/j.jacc.2017.11.055
    • Ercig, B., Wichapong, K., Reutelingsperger, C. P. M., Vanhoorelbeke, K., Voorberg, J., & Nicolaes, G. A. F. (2018). Insights into 3D Structure of ADAMTS13: A Stepping Stone towards Novel Therapeutic Treatment of Thrombotic Thrombocytopenic Purpura. Thrombosis and Haemostasis, 118(1), 28-41. https://doi.org/10.1160/TH17-06-0404
  • 2017
    • Aarts, S. A. B. M., Seijkens, T. T. P., Kusters, P. J. H., van der Pol, S. M. A., Zarzycka, B., Heijnen, P. D. A. M., Beckers, L., den Toom, M., Gijbels, M. J. J., Boon, L., Weber, C., de Vries, H. E., Nicolaes, G. A. F., Dijkstra, C. D., Kooij, G., & Lutgens, E. (2017). Inhibition of CD40-TRAF6 interactions by the small molecule inhibitor 6877002 reduces neuroinflammation. Journal of Neuroinflammation, 14, [105]. https://doi.org/10.1186/s12974-017-0875-9
    • von Hundelshausen, P., Agten, S. M., Eckardt, V., Blanchet, X., Schmitt, M. M., Ippel, H., Neideck, C., Bidzhekov, K., Leberzammer, J., Wichapong, K., Faussner, A., Drechsler, M., Grommes, J., van Geffen, J. P., Li, H., Ortega-Gomez, A., Megens, R. T. A., Naumann, R., Dijkgraaf, I., ... Weber, C. (2017). Chemokine interactome mapping enables tailored intervention in acute and chronic inflammation. Science Translational Medicine, 9(384), [eaah6650]. https://doi.org/10.1126/scitranslmed.aah6650
    • van Smaalen, T. C., Beurskens, D. M. H., Hoogland, E. R. P., Winkens, B., Christiaans, M. H. L., Reutelingsperger, C. P., van Heurn, L. W. E., & Nicolaes, G. A. F. (2017). Presence of Cytotoxic Extracellular Histones in Machine Perfusate of Donation After Circulatory Death Kidneys. Transplantation, 101(4), e93-e101. https://doi.org/10.1097/TP.0000000000001590
  • 2016
    • Wichapong, K., Alard, J. -E., Ortega-Gomez, A., Weber, C., Hackeng, T. M., Soehnlein, O., & Nicolaes, G. A. F. (2016). Structure-Based Design of Peptidic Inhibitors of the Interaction between CC Chemokine Ligand 5 (CCL5) and Human Neutrophil Peptides 1 (HNP1). Journal of Medicinal Chemistry, 59(9), 4289-4301. https://doi.org/10.1021/acs.jmedchem.5b01952
    • Miglianico, M., Nicolaes, G. A. F., & Neumann, D. (2016). Pharmacological Targeting of AMP-Activated Protein Kinase and Opportunities for Computer-Aided Drug Design. Journal of Medicinal Chemistry, 59(7), 2879-2893. https://doi.org/10.1021/acs.jmedchem.5b01201
    • Labbe, C. M., Kuenemann, M. A., Zarzycka, B., Vriend, G., Nicolaes, G. A. F., Lagorce, D., Miteva, M. A., Villoutreix, B. O., & Sperandio, O. (2016). iPPI-DB: an online database of modulators of protein-protein interactions. Nucleic Acids Research, 44(D1), D542-D547. https://doi.org/10.1093/nar/gkv982
    • Zarzycka, B., Kuenemann, M. A., Miteva, M. A., Nicolaes, G. A. F., Vriend, G., & Sperandio, O. (2016). Stabilization of protein-protein interaction complexes through small molecules. Drug Discovery Today, 21(1), 48-57. https://doi.org/10.1016/j.drudis.2015.09.011
  • 2015
    • Alard, J-E., Ortega-Gomez, A., Wichapong, K., Bongiovanni, D., Horckmans, M., Megens, R. T. A., Leoni, G., Ferraro, B., Rossaint, J., Paulin, N., Ng, J., Ippel, H., Suylen, D., Hinkel, R., Blanchet, X., Gaillard, F., D'Amico, M., von Hundelshausen, P., Zarbock, A., ... Soehnlein, O. (2015). Recruitment of classical monocytes can be inhibited by disturbing heteromers of neutrophil HNP1 and platelet CCL5. Science Translational Medicine, 7(317), [317ra196]. https://doi.org/10.1126/scitranslmed.aad5330
    • De Waelheyns, E., Segers, K., Sardis, M. F., Anne, J., Nicolaes, G. A. F., & Economou, A. (2015). Identification of small-molecule inhibitors against SecA by structure-based virtual ligand screening. Journal of Antibiotics, 68(11), 666-673. https://doi.org/10.1038/ja.2015.53
    • Wildhagen, K. C. A. A., Wiewel, M. A., Schultz, M. J., Horn, J., Schrijver, R., Reutelingsperger, C. P. M., van der Poll, T., & Nicolaes, G. A. F. (2015). Extracellular histone H3 levels are inversely correlated with antithrombin levels and platelet counts and are associated with mortality in sepsis patients. Thrombosis Research, 136(3), 542-547. https://doi.org/10.1016/j.thromres.2015.06.035
    • van den Berg, S. M., Seijkens, T. T. P., Kusters, P. J. H., Zarzycka, B., Beckers, L., den Toom, M., Gijbels, M. J. J., Chatzigeorgiou, A., Weber, C., de Winther, M. P. J., Chavakis, T., Nicolaes, G. A. F., & Lutgens, E. (2015). Blocking CD40-TRAF6 interactions by small-molecule inhibitor 6860766 ameliorates the complications of diet-induced obesity in mice. International Journal of Obesity, 39(5), 782-790. https://doi.org/10.1038/ijo.2014.198
    • Zarzycka, B., Nicolaes, G. A. F., & Lutgens, E. (2015). Targeting the adaptive immune system: new strategies in the treatment of atherosclerosis. Expert Review of Clinical Pharmacology , 8(3), 297-313. https://doi.org/10.1586/17512433.2015.1025052
    • Zarzycka, B., Seijkens, T., Nabuurs, S. B., Ritschel, T., Grommes, J., Soehnlein, O., Schrijver, R., van Tiel, C. M., Hackeng, T. M., Weber, C., Giehler, F., Kieser, A., Lutgens, E., Vriend, G., & Nicolaes, G. A. F. (2015). Discovery of Small Molecule CD40-TRAF6 Inhibitors. Journal of Chemical Information and Modeling, 55(2), 294-307. https://doi.org/10.1021/ci500631e
    • Du, J., Wichapong, K., Hackeng, T. M., & Nicolaes, G. A. F. (2015). Molecular simulation studies of human coagulation factor VIII C domain-mediated membrane binding. Thrombosis and Haemostasis, 113(2), 373-384. https://doi.org/10.1160/TH14-02-0180
    • Körver-Keularts, I. M. L. W., de Visser, M., Bakker, H. D., Wanders, R. J. A., Vansenne, F., Scholte, H. R., Dorland, L., Nicolaes, G. A. F., Spaapen, L. M. J., Smeets, H. J. M., Hendrickx, A. T. M., & van den Bosch, B. J. C. (2015). Two Novel Mutations in the SLC25A4 Gene in a Patient with Mitochondrial Myopathy.JIMD reports, 22, 39-45. https://doi.org/10.1007/8904_2015_409
  • 2014
    • Du, J., Nicolaes, G. A. F., Kruijswijk, D., Versloot, M., van der Poll, T., & van 't Veer, C. (2014). The structure function of the death domain of human IRAK-M. Cell Communication and Signaling, 12, [77]. https://doi.org/10.1186/s12964-014-0077-3
    • Chaves, R. C., Dahmane, S., Odorico, M., Nicolaes, G. A. F., & Pellequer, J-L. (2014). Factor Va alternative conformation reconstruction using atomic force microscopy. Thrombosis and Haemostasis, 112(6), 1167-1173. https://doi.org/10.1160/TH14-06-0481
    • Studer, R. A., Opperdoes, F. R., Nicolaes, G. A. F., Mulder, A. B., & Mulder, R. (2014). Understanding the functional difference between growth arrest-specific protein 6 and protein S: an evolutionary approach. Open Biology, 4(10), [140121]. https://doi.org/10.1098/rsob.140121
    • Wildhagen, K. C. A. A., Schrijver, R., Beckers, L., ten Cate, H., Reutelingsperger, C. P. M., Lutgens, E., & Nicolaes, G. A. F. (2014). Effects of Exogenous Recombinant APC in Mouse Models of Ischemia Reperfusion Injury and of Atherosclerosis. PLOS ONE, 9(7), [e101446]. https://doi.org/10.1371/journal.pone.0101446
    • Sperandio, O., Wildhagen, K. C. A. A., Schrijver, R., Wielders, S., Villoutreix, B. O., & Nicolaes, G. A. F. (2014). Identification of novel small molecule inhibitors of activated protein C. Thrombosis Research, 133(6), 1105-1114. https://doi.org/10.1016/j.thromres.2014.01.026
    • Chatzigeorgioua, A., Seijkens, T., Zarzycka, B., Engel, D., Poggi, M., van den Berg, S., van den Berg, S., Soehnlein, O., Winkels, H., Beckers, L., Lievens, D., Driessen, A., Kusters, P., Biessen, E., Garcia-Martin, R., Ameln, A. K., Gijbels, M., Noelle, R., Boon, L., ... Lutgens, E. (2014). Blocking CD40-TRAF6 signaling is a therapeutic target in obesity-associated insulin resistance. Proceedings of the National Academy of Sciences of the United States of America, 111(7), 2686-2691. https://doi.org/10.1073/pnas.1400419111
    • Wildhagen, K. C. A. A., Garcia de Frutos, P., Reutelingsperger, C. P., Schrijver, R., Areste, C., Ortega-Gomez, A., Deckers, N. M., Hemker, H. C., Soehnlein, O., & Nicolaes, G. A. F. (2014). Nonanticoagulant heparin prevents histone-mediated cytotoxicity in vitro and improves survival in sepsis. Blood, 123(7), 1098-1101. https://doi.org/10.1182/blood-2013-07-514984
    • Nicolaes, G. A. F., Kulharia, M., Voorberg, J., Kaijen, P. H., Wroblewska, A., Wielders, S., Schrijver, R., Sperandio, O., & Villoutreix, B. O. (2014). Rational design of small molecules targeting the C2 domain of coagulation factor VIII. Blood, 123(1), 113-120. https://doi.org/10.1182/blood-2013-05-503227
    • Du, J., Bleylevens, I. W. M., Bitorina, A., Wichapong, K., & Nicolaes, G. A. F. (2014). Optimization of compound ranking for structure-based virtual ligand screening using an established FRED-Surflex consensus approach. Chemical Biology & Drug Design, 83(1), 37-51. https://doi.org/10.1111/cbdd.12202
  • 2013
    • Schuijt, T. J., Bakhtiari, K., Daffre, S., DePonte, K., Wielders, S. J. H., Marquart, J. A., Hovius, J. W., van der Poll, T., Fikrig, E., Bunce, M. W., Camire, R. M., Nicolaes, G. A. F., Meijers, J. C. M., & van 't Veer, C. (2013). Factor Xa Activation of Factor V Is of Paramount Importance in Initiating the Coagulation System: Lessons From a Tick Salivary Protein. Circulation, 128(3), 254-266. https://doi.org/10.1161/CIRCULATIONAHA.113.003191
  • 2012
    • Sanders, M. P. A., Barbosa, A. J. M., Zarzycka, B., Nicolaes, G. A. F., Klomp, J. P. G., de Vlieg, J., & Del Rio, A. (2012). Comparative Analysis of Pharmacophore Screening Tools. Journal of Chemical Information and Modeling, 52(6), 1607-1620. https://doi.org/10.1021/ci2005274
    • Mencarelli, C., Bode, G. H., Losen, M., Kulharia, M., Molenaar, P. C., Veerhuis, R., Steinbusch, H. W. M., De Baets, M. H., Nicolaes, G. A. F., & Martinez-Martinez, P. (2012). Goodpasture Antigen-binding Protein/Ceramide Transporter Binds to Human Serum Amyloid P-Component and Is Present in Brain Amyloid Plaques. Journal of Biological Chemistry, 287(18), 14897-14911. https://doi.org/10.1074/jbc.M111.299545
  • 2011
    • Wildhagen, K. C. A. A., Lutgens, E., Loubele, S. T. G. B., ten Cate, H., & Nicolaes, G. A. F. (2011). The structure-function relationship of activated protein C Lessons from natural and engineered mutations. Thrombosis and Haemostasis, 106(6), 1034-1045. https://doi.org/10.1160/TH11-08-0522
    • Ungethum, L., Kenis, H., Nicolaes, G. A., Autin, L., Stoilova-McPhie, S., & Reutelingsperger, C. P. M. (2011). Engineered Annexin A5 Variants Have Impaired Cell Entry for Molecular Imaging of Apoptosis Using Pretargeting Strategies. Journal of Biological Chemistry, 286(3), 1903-1910. https://doi.org/10.1074/jbc.M110.163527
    • Gerards, M., van den Bosch, B. J. C., Danhauser, K., Serre, V., van Weeghel, M., Wanders, R. J. A., Nicolaes, G. A. F., Sluiter, W., Schoonderwoerd, K., Scholte, H. R., Prokisch, H., Rötig, A., de Coo, I. F. M., & Smeets, H. J. M. (2011). Riboflavin-responsive oxidative phosphorylation complex I deficiency caused by defective ACAD9: new function for an old gene. Brain, 134(Pt 1), 210-219. https://doi.org/10.1093/brain/awq273
  • 2010
    • Nicolaes, G. A. F., Bock, P. E., Segers, K., Wildhagen, K. C. A. A., Dahlback, B., & Rosing, J. (2010). Inhibition of Thrombin Formation by Active Site Mutated (S360A) Activated Protein C. Journal of Biological Chemistry, 285(30), 22888-22898. https://doi.org/10.1074/jbc.M110.131029
    • Liu, Z., Lin, L., Yuan, C., Nicolaes, G. A. F., Chen, L., Meehan, E. J., Furie, B., Furie, B. C., & Huang, M. (2010). Trp(2313)-His(2315) of Factor VIII C2 Domain Is Involved in Membrane Binding STRUCTURE OF A COMPLEX BETWEEN THE C2 DOMAIN AND AN INHIBITOR OF MEMBRANE BINDING. Journal of Biological Chemistry, 285(12), 8824-8829. https://doi.org/10.1074/jbc.M109.080168